The following research objectives will be carried out. Using a potent GnRH antagonist ((Ac-dehydro-Pro1, pC1-d-Phe2, D-Trp3,6)-N-Alpha-MeLeu-GnRH) we will examine the relative dependency of FSH and LH secretion rates on GnRH. We will also determine if follicular fluid can be shown to suppress LH secretion in vivo as it does in vitro under GnRH stimulation. Gonadal feedback control of FSH and LH will be examined in several experiments. The role of estradiol feedback in the delay of LH rise following ovariectomy will be tested. The necessity of the dorsal anterior hypothalamic area (DAHA) for the singular rise of FSH during the secondary surge or following ovariectomy will be investigated. We will also determine if the relative inadequacy of estradiol in triggering a primary FSH surge is due to its inadequacy in first suppressing serum FSH in ovarectomized recipients. Ovarian translantation models will also be used to study FSH and LH regulation. Mechanisms of stress interference with FSH and LH secretion will be investigated by examining the intervention of the adrenal-pituitary axis in the acute LH and FSH response to loss of testis feedback. The role of prolactin and progesterone in the blockade of ovulation by pentobarbital administration will be studied. The effect of neonatal hormone treatment on several sexually dimorphic aspects of tonic regulation of LH and FSH will be examined. In terms of health-related implications, the world faces the problem of enhancing fertility in some cases and preventing it under other circumstances. We feel that a series of approaches, such as we represent, is called for in attacking the multiple problems faced by society with respect to population.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD007504-12A1
Application #
3310698
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1977-06-01
Project End
1989-11-30
Budget Start
1985-04-01
Budget End
1985-11-30
Support Year
12
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
Schools of Arts and Sciences
DUNS #
City
Evanston
State
IL
Country
United States
Zip Code
60208
Szabo, M; Kilen, S M; Nho, S J et al. (2000) Progesterone receptor A and B messenger ribonucleic acid levels in the anterior pituitary of rats are regulated by estrogen. Biol Reprod 62:95-102
Szabo, M; Kilen, S M; Saberi, S et al. (1998) Antiprogestins suppress basal and activin-stimulated follicle-stimulating hormone secretion in an estrogen-dependent manner. Endocrinology 139:2223-8
Schwartz, N B; Szabo, M; Verina, T et al. (1998) Hypothalamic-pituitary-gonadal axis in the mutant weaver mouse. Neuroendocrinology 68:374-85
Ringstrom, S J; Szabo, M; Kilen, S M et al. (1997) The antiprogestins RU486 and ZK98299 affect follicle-stimulating hormone secretion differentially on estrus, but not on proestrus. Endocrinology 138:2286-90
Woodruff, T K; Besecke, L M; Groome, N et al. (1996) Inhibin A and inhibin B are inversely correlated to follicle-stimulating hormone, yet are discordant during the follicular phase of the rat estrous cycle, and inhibin A is expressed in a sexually dimorphic manner. Endocrinology 137:5463-7
Knox, K L; Ringstrom, S J; Szabo, M et al. (1996) RU486 on an estrogen background blocks the rise in serum follicle-stimulating hormone induced by antiserum to inhibin or ovariectomy. Endocrinology 137:1226-32
Szabo, M; Knox, K L; Ringstrom, S J et al. (1996) Mechanism of the inhibitory action of RU486 on the secondary follicle-stimulating hormone surge. Endocrinology 137:85-9
McAndrews, J M; Ringstrom, S J; Dahl, K D et al. (1994) Corticosterone in vivo increases pituitary follicle-stimulating hormone (FSH)-beta messenger ribonucleic acid content and serum FSH bioactivity selectively in female rats. Endocrinology 134:158-63
Luderer, U; Schwartz, N B (1994) Acute changes in pulsatile LH and FSH secretion after ovariectomy in rats: treatment with oestradiol for 24 h suppresses LH, but not FSH, for at least 48 h. J Reprod Fertil 100:613-21
Knox, K L; Ringstrom, S J; Schwartz, N B (1993) RU486 blocks the effects of inhibin antiserum or luteinizing hormone on the secondary follicle-stimulating hormone surge. Endocrinology 133:277-83

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